1. In this randomized clinical trial, patients on hemodialysis who received a vitamin D receptor activator (VDRA) did not have better cardiovascular health compared to those with placebo.
2. Patients receiving active vitamin D did not have reduced mortality.
Evidence Rating Level: 1 (Excellent)
Study Rundown: Patients with advanced chronic kidney disease (CKD) on hemodialysis are at greater risk for cardiovascular disease, and impaired activation of vitamin D by the kidneys may contribute to this increased risk. Though studies have shown benefits of vitamin D receptor activators (VDRAs) like alfacalcidol for reducing cardiovascular risk, it is not clear if they reduce risk in CKD patients on dialysis. In this open-label, randomized controlled trial, patients on dialysis who received oral alfacalcidol did not have reduced risk of composite cardiac events compared to controls. In addition, there was no difference in mortality between groups. The number of adverse events were similar.
Unfortunately, these results are in line with previous studies such as PRIMO and OPERA that showed that oral paricalcitriol did not have cardiovascular benefit. Though the control group was allowed to take VDRAs if mandated by guidelines, suggesting one confounding factor, the investigators attempted to address this issue by selecting patients with intact PTH levels. In addition, post-hoc power analyses suggested the study may have been underpowered to sufficiently detect differences in the primary and secondary outcomes.
Click to read the study in JAMA
Relevant Reading: Analysis of the kinetics of the parathyroid hormone, and of associated patient outcomes, in a cohort of haemodialysis patients
In-Depth [randomized controlled trial]: In the Japan Dialysis Active Vitamin D (J-DAVID) trial, 976 patients with CKD on maintenance hemodialysis with intact PTH levels (less than or equal to 180 pg/mL) were recruited from 207 Japanese dialysis centers from 2008 to 2011. They were randomized 1:1 to receive 0.5 µg of oral alfacalcidol or care as usual. The control group was asked to avoid other VDRAs but was allowed to receive them if warranted by guidelines of the Japanese Society for Dialysis Therapy. The primary outcome was a composite of fatal and nonfatal cardiovascular events, including myocardial infarction, congestive heart failure requiring hospitalization, stroke, aortic dissection/rupture, amputation of ischemic limb, sudden cardiac event, coronary interventions, and lower limb artery interventions. The secondary outcome was all-cause death. During a median follow-up of 4.0 years, the primary outcome occurred in 103 patients (21.1%) in the intervention group and 85 patients (19.9%) in the control group (absolute difference 3.25%; CI95 -1.75% to 8.24%). There was no significant difference between the intervention and control group in the secondary outcome of all-cause death (HR 1.12; CI95 0.83-1.52). The adjusted hazard ratios for the primary outcomes were 1.32 (CI95 0.96-1.82) and 1.34 (CI95 0.97-1.83) when the per-protocol set and the modified per-protocol set were analyzed. The numbers of significant adverse events were also similar between both groups.
Image: PD
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